We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin.
- Authors
Verma, Akash H.; Richardson, Jonathan P.; Chunsheng Zhou; Coleman, Bianca M.; Moyes, David L.; Ho, Jemima; Huppler, Anna R.; Ramani, Kritika; McGeachy, Mandy J.; Mufazalov, Ilgiz A.; Waisman, Ari; Kane, Lawrence P.; Biswas, Partha S.; Hube, Bernhard; Naglik, Julian R.; Gaffen, Sarah L.
- Abstract
Candida albicans is a dimorphic commensal fungus that causes severe oral infections in immunodeficient patients. Invasion of C. albicans hyphae into oral epithelium is an essential virulence trait. Interleukin-17 (IL-17) signaling is required for both innate and adaptive immunity to C. albicans. During the innate response, IL-17 is produced by γδ T cells and a poorly understood population of innate-acting CD4+αβ T cell receptor (TCRαβ) + cells, but only the TCRαβ+ cells expand during acute infection. Confirming the innate nature of these cells, the TCR was not detectably activated during the primary response, as evidenced by Nur77eGFP mice that report antigen-specific signaling through the TCR. Rather, the expansion of innate TCRαβ+ cells was driven by both intrinsic and extrinsic IL-1R signaling. Unexpectedly, there was no requirement for CCR6/CCL20-dependent recruitment or prototypical fungal pattern recognition receptors. However, C. albicans mutants that cannot switch from yeast to hyphae showed impaired TCRαβ+ cell proliferation and Il17a expression. This prompted us to assess the role of candidalysin, a hyphal-associated peptide that damages oral epithelial cells and triggers production of inflammatory cytokines including IL-1. Candidalysin-deficient strains failed to up-regulate Il17a or drive the proliferation of innate TCRαβ+ cells. Moreover, candidalysin signaled synergistically with IL-17, which further augmented the expression of IL-1α/β and other cytokines. Thus, IL-17 and C. albicans, via secreted candidalysin, amplify inflammation in a self-reinforcing feed-forward loop. These findings challenge the paradigm that hyphal formation per se is required for the oral innate response and demonstrate that establishment of IL-1– and IL-17–dependent innate immunity is induced by tissue-damaging hyphae.
- Publication
Science Immunology, 2017, Vol 2, Issue 17, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.aam8834